Successful treatment of temporomandibular joint (TMJ) disorders is a major unmet clinical need. The objective is to generate functional tissue engineered TMJ articular cartilage for the treatment of TMJ disorders. There are several major technical hurdles that still must be overcome for the development of clinically useful tissue engineered cartilage, including the generation of functional mechanical properties, and availability of an appropriate cell source. Recent studies indicate we have the components necessary to develop a TMJ cartilage with the potential to be used for implantation and TMJ repair. Our objective is to utilize these advances (cell source, bioreactor growth systems, scaffolds) to generate TMJ articular cartilage appropriate for implantation and repair of the TMJ. The overall hypothesis for this project is that proliferated cells, polymer scaffolds with functional tensile properties and bioreactor growth conditions, can be combined to form tissue engineered constructs with functional properties similar to native TMJ articular cartilage. To test this hypothesis and to achieve the stated goal,we have 3 Specific Aims. Specific Aim 1: Characterize the TMJ mandibular articular cartilage and identify a scaffold that can provide functional tensile properties similar to TMJ articular cartilage, and support cell attachment. Specific Aim 2. Determine the ability of TMJ articular cartilage cells and hMSCs to proliferate, and to maintain or modulate their differentiation to a fibrocartilage phenotype appropriate for synthesis of TMJ articular cartilage. Specific Aim 3: Identify and optimize bioreactor growth conditions for cell-seeded scaffolds to generate constructs similar to native TMJ articular cartilage. The successful outcome of this multidisciplinary and interdisciplinary study has several important critical outcomes to the development of a successful TMJ cartilage repair methodology. Critically, these studies will lead to translational research, where these tissue engineered constructs will be assessed in vivo for their ability to successfully repair TMJ articular cartilage [unreadable] [unreadable] [unreadable]